Lee Y S, Choi Y H, Kim T K, Ryu K H, Lee B-Y, Lee M G
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Xenobiotica. 2010 Feb;40(2):129-37. doi: 10.3109/00498250903380975.
The area under the curve (AUC) of mirodenafil after intravenous administration in diabetes mellitus induced by streptozotocin (DMIS) rats was significantly smaller (by 28.0 %) than the control value, and the AUC(SK3541)/AUC(mirodenafil) ratio was significantly greater (by 130 %) in DMIS rats. This may be explained by the significantly faster hepatic CL(int) of mirodenafil, owing to increased hepatic CYP1A, CYP2B1/2, CYP2D, and CYP3A expression, and a faster hepatic blood flow rate, compared with control values. The AUC of mirodenafil after oral administration was comparable between DMIS and control rats, possibly because of the comparable intestinal CL(int), which may be attributable to increased CYP1A2 expression and decreased CYP2D expression in the intestines of DMIS rats.
在链脲佐菌素诱导的糖尿病（DMIS）大鼠中，米罗地那非静脉给药后的曲线下面积（AUC）显著小于对照值（降低了28.0%），并且DMIS大鼠中AUC(SK3541)/AUC(米罗地那非)比值显著更高（升高了130%）。这可能是由于与对照值相比，米罗地那非的肝脏内在清除率（CL(int)）显著更快，这是由于肝脏CYP1A、CYP2B1/2、CYP2D和CYP3A表达增加以及肝脏血流速度更快所致。DMIS大鼠和对照大鼠口服米罗地那非后的AUC相当，这可能是因为肠道CL(int)相当，这可能归因于DMIS大鼠肠道中CYP1A2表达增加和CYP2D表达降低。
